Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (Ϸ22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumorderived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.biomarker ͉ miR-141 ͉ plasma ͉ serum ͉ prostate cancer T he development of minimally invasive tests for the detection and monitoring of common epithelial malignancies could greatly reduce the worldwide health burden of cancer (1). Although conventional strategies for blood-based biomarker discovery (e.g., using proteomic technologies) have shown promise, the development of clinically validated cancer detection markers remains an unmet challenge for many common human cancers (2). New approaches that can complement and improve on current strategies for cancer detection are urgently needed.MicroRNAs (miRNAs) are small (typically Ϸ22 nt in size) regulatory RNA molecules that function to modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes (3, 4). We hypothesized that miRNAs could be an ideal class of blood-based biomarkers for cancer detection because: (i) miRNA expression is frequently dysregulated in cancer (5, 6), (ii) expression patterns of miRNAs in human cancer appear to be tissue-specific (7), and (iii) miRNAs have unusually high stability in formalin-fixed tissues (8-10). This third point led us to speculate that miRNAs may have exceptional stability in plasma and serum as well. We show here that miRNAs are in fact present in clinical samples of plasma and serum in a remarkably stable form. Furthermore, we establish proof-ofprinciple for blood-based miRNA cancer detection by using both a xenograft model system and clinical serum specimens from patients with prostate cancer. Our results lay the foundation for the development of miRNAs as a novel class of blood-based cancer biomarkers and raise provocative questions regarding the mechanism of stability and potential biological function of circulating miRNAs. Results Identification and Molecular Cloning of Endogenous miRNAs fromHuman Plasma. Prior reports have suggested that RNA from human plasma (the noncellular component of blood remaining after removing cells by centrifugation) is largely of low molecular weight (11). W...

Bioconductor: open software development for computational biology and bioinformatics

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.

No abstract

Cancer epidemiologists are regularly asked by members of the interested public about possible associations between suspected carcinogens and apparently increased small-area cancer incidence rates. Frequently, no systematic incidence differences can be demonstrated. Under these circumstances, the large extent of random variation in small-area tumour incidence rates is difficult to convey. Nevertheless, it is necessary to address public concerns about suspected cancer clusters. To facilitate explanations about random variation of tumour incidence given to the public by cancer epidemiologists, we implemented a software tool in R for small-area simulation of cancer incidences. The tool simulates a small village population with graphical representation of streets and houses. Program parameters include sample size, age distribution, and number of cancer entities with respective incidence rates and survival time distributions. Our software tool can be used effectively for numerical and graphical visualisation of small-area tumour incidence rates. The explanation of basic epidemiological concepts to members of the public can help to increase public motivation and support for population-based cancer registration. Our simulation tool can be used to support this goal. It will be made available for free download in due course. References:Ihaka, R, Gentleman, R.R (1996). A Language for Data Analysis and Graphics. J Comput Graph Stat 5, 299-314. P1.20: Breast Cancer in the Federal States of Rhineland-Palatinate and SaarlandIrene Schmidtmann*, Christa Stegmaier, Gabriele Husmann, Anneliese Krtschil, Rainer Müller, Gerhard Seebauer * Corresponding Author: Krebsregister Rheinland-Pfalz, Institut für Med. Biometrie, Epidemiologie und Informatik, Mainz email: schmidtm@imbei.uni-mainz.deReliable incidence data are required to evaluate effects of breast cancer screening programs. The cancer registries in RhinelandPalatinate and Saarland among others have such data. We calculated age standardized incidence rates and mortality rates using the European standard population. 13.727 cases from Saarland diagnosed between 1980 and 2000 and 7.072 cases from Rhineland-Palatinate diagnosed between 1998 and 2000 were included in the analysis. Age standardized incidence in Saarland increased from 76 per 100.000 in 1980 to 110 per 100.000 in 2000 while age standardized mortality increased from 29 per 100.000 to 34 per 100.000 during the same period. Both incidence and mortality are slightly lower in Rhineland-Palatinate during the time period covered in both registries. Information on UICC stage is available in 66 % of cases from Saarland and in 87 % of cases from Rhineland-Palatinate. In the early 1980s 3 % of cases were diagnosed in situ, 17 % in UICC stage 1. In the late 1990s 7 % of cases in Saarland and 4 % of cases in Rhineland-Palatinate were diagnosed in situ, UICC stage 1 was found among 27 % in Saarland and among 32 % in RhinelandPalatinate. Stage distribution varies with age, place of residence, and histological subtype. Ductal carcinom...